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Literature review and methodological considerations for understanding circulating risk biomarkers following trauma exposure

Molecular Psychiatry volume 25, pages 1986–1999 (2020)Cite this article

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Abstract

Exposure to traumatic events is common. While many individuals recover following trauma exposure, a substantial subset develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as posttraumatic stress, major depression, and regional or widespread chronic musculoskeletal pain. APNS cause substantial burden to the individual and to society, causing functional impairment and physical disability, risk for suicide, lost workdays, and increased health care costs. Contemporary treatment is limited by an inability to identify individuals at high risk of APNS in the immediate aftermath of trauma, and an inability to identify optimal treatments for individual patients. Our purpose is to provide a comprehensive review describing candidate blood-based biomarkers that may help to identify those at high risk of APNS and/or guide individual intervention decision-making. Such blood-based biomarkers include circulating biological factors such as hormones, proteins, immune molecules, neuropeptides, neurotransmitters, mRNA, and noncoding RNA expression signatures, while we do not review genetic and epigenetic biomarkers due to other recent reviews of this topic. The current state of the literature on circulating risk biomarkers of APNS is summarized, and key considerations and challenges for their discovery and translation are discussed. We also describe the AURORA study, a specific example of current scientific efforts to identify such circulating risk biomarkers and the largest study to date focused on identifying risk and prognostic factors in the aftermath of trauma exposure.

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Fig. 1: Circulating blood-based risk biomarkers that have been assessed in previous studies for their ability to predict the development of adverse posttraumatic neuropsychiatric sequelae (APNS).
Fig. 2: Key steps (top) and methodological considerations (bottom) in the discovery of circulating blood-based risk biomarkers of adverse posttraumatic neuropsychiatric sequelae (APNS).
Fig. 3: The AURORA study is an on-going longitudinal cohort study assessing APNS development following trauma exposure. Individuals are enrolled in the Emergency Department and followed over the course of a year.

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Acknowledgements

We acknowledge Elizabeth Moreton and Michelle Cawley from the University of North Carolina Health Sciences Library for support in performing the literature search for this review article. SDL is supported by NIH K01AR071504, SAM is supported by NIH R01AR064700 and U01MH110925, KCK is supported by NIH R01MH106595, R01MH101269, U01MH110925, and T32MH017119, KJR is supported by NIH U01MH110925, R01MH071537, R01MH094757, and R01MH106595.

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Authors and Affiliations

  1. Institute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, USA

    Sarah D. Linnstaedt, Anthony S. Zannas & Samuel A. McLean

  2. Department of Anesthesiology, University of North Carolina, Chapel Hill, NC, USA

    Sarah D. Linnstaedt & Samuel A. McLean

  3. Departments of Psychiatry and Genetics, University of North Carolina, Chapel Hill, NC, USA

    Anthony S. Zannas

  4. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

    Anthony S. Zannas

  5. Department of Emergency Medicine, University of North Carolina, Chapel Hill, NC, USA

    Samuel A. McLean

  6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Karestan C. Koenen

  7. Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA

    Kerry J. Ressler

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Correspondence to Kerry J. Ressler.

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Conflict of interest

KJR provides fee-for-service consultation for Johnson & Johnson, Verily, and Alkermes. He has received sponsored research unrelated to this work from Brainsway and Takeda. He also holds patents for a number of targets related to improving extinction of fear, however, he has received no equity or income within the last 3 years related to these. He receives or has received research funding from NIMH, NIAAA, HHMI, NARSAD, and the Burroughs Wellcome Foundation. The other authors declare no conflicts of interest.

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Linnstaedt, S.D., Zannas, A.S., McLean, S.A. et al. Literature review and methodological considerations for understanding circulating risk biomarkers following trauma exposure. Mol Psychiatry 25, 1986–1999 (2020). https://doi.org/10.1038/s41380-019-0636-5

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